The Río Santa Cruz is the last free-flowing glacial river in Argentine Patagonia, originating in the Southern Patagonian Ice Field and running approximately 360 kilometers before emptying into the Atlantic Ocean at Puerto Santa Cruz. Fed by Lago Argentino, it crosses the full width of the province of Santa Cruz through open Patagonian steppe. The river carries a distinctive turquoise color characteristic of glacial meltwater, and its volume makes it one of the most significant waterways in Argentina.

Throughout its entire length the river is rated Class I, meaning there are no rapids. The current provides consistent downstream momentum, and paddlers generally find that little active paddling is required to maintain progress. Wind is a significant factor on this river — the Patagonian steppe offers no shelter, and wave action can develop in exposed sections, particularly in the lower reaches where tidal influence from the sea also creates chop. Guides authorized by the Argentine Naval Prefecture accompany commercial expeditions.

The full river expedition runs roughly 350 kilometers by kayak over seven days, starting from the area near Lago Argentino (with put-ins at locations such as Estancia Bonn Accord) and finishing at Puerto Santa Cruz on the Atlantic coast. Shorter day trips are also available near El Calafate, with one popular guided outing covering approximately 15 kilometers on the upper section of the river. Accommodation on the multi-day expedition combines wild camping (four nights) with cabin or hotel stays (two nights).

The river has considerable historical significance. It was first noted by the pilot Serrano during Magellan's 1520 expedition, and was subsequently explored by the Viedma brothers, Carlos Moyano, Charles Darwin, and Francisco Pascasio Moreno, among others. The surrounding landscape is home to the indigenous Aonikenk people's cultural heritage. Wildlife and the open steppe scenery accompany paddlers throughout the journey. The river has also attracted fly fishers targeting steelhead and sea trout, which are present in the system. The lower river is notably wide and can appear imposing in scale.

The river has been the subject of conservation concern due to proposed hydroelectric development, and at the time of writing remains largely intact and undammed.